This proposal is to study insulin secretion and the metabolic response of recipient rats made diabetic by streptozotocin after transplantation of fetal pancreases. Diabetes follows intravenous injection of streptozotocin in doses of 65 mg/kg body weight. After diabetes is established fetal pancreases of syngeneic strain will be placed beneath the kidney capsule and the metabolic response of the recipient rat will be measured by blood glucose concentration and urine volume and glucose content. After establishment of a reproducible model of response in syngeneic transfers, the results of allogeneic transfer in in-bred strains of rats of known histoincompatibility will be determined. Effects of overcoming rejection across histocompatibility barriers by blocking antibody will be tested. Methods for improving the capacity of fetal rat pancreases to reverse diabetes will be worked out. This includes a renal vein -portal vein shunt operation and in vivo culture of fetal pancreases in normal syngeneic rats before transfer to diabetic animals. Cryopreservation methods have been worked out and the functional capacity of such cryopreserved pancreases will be determined. BIBLIOGRAPHIC REFERENCES: Brown, J., W. Clark, I. Molnar and Y. Mullen. Fetal Pancreas Transplantation for Reversal of Streptozotocin-induced Diabetes in Rats. Diabetes 25:56, 1976. Mullen, Y., W.R. Clark, J. Kemp, I.G. Molnar and J. Brown. Reversal of Experimental Diabetes by Fetal Rat Pancreases. II. Critical Procedures for Transplantation. Transplantation Proceedings, 1977, in press.